PROJECT SUMMARY Precision medicine is emerging as an approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. While some limited advances in precision medicine have been made in the field of oncology, precision medicine is not in broad practice. Precision medicine has become an initiative of the National Institutes of Health (NIH) and its partners. Development of methods of patient-specific biomarker imaging to guide and monitor patient-specific therapies will be needed to move forward this new NIH initiative. A trained physician-scientist workforce is key to taking advantage of these new developments. Precision imaging advances are interdisciplinary with technology innovations crossing the physical, computational, and biological sciences. These studies start with preclinical mechanistic inquiries using targeted pathology-based imaging and then expand into human subjects. Human studies include safety testing and the Food and Drug Administration's (FDA) Investigational New Drug (IND) and Device Exemption (IDE) process. The ultimate goal is to make research innovations widely available to the public and the entire practicing medical community through commercialization. Although this ?bench-to-bedside? process has been widely acclaimed, there remains a knowledge gap in the medical imaging research community as to how to take preclinical research into humans, and how to then take these innovations to the public. Moreover, clinical scientists ? residents and fellows ? often lack the understanding to navigate research regulatory requirements as well as the knowledge base to understand or perform preclinical research that will inform the mechanism of innovation. A completely new educational and creative paradigm is required to better prepare future imaging scientists for the challenges of the NIH Precision Medicine Initiative. Interdisciplinary teams of physician-scientists must work together at the interfaces of biology, technology, and medicine, and physicians must be educated to work to bring innovation through the FDA regulatory processes, into human subjects and to the public through commercialization. In this application, we propose a model of education unlike any other for resident and fellow physician-scientists that will provide them with a two-year training program consisting of a) a required curriculum (year 1) that covers not only training in the ethics, regulatory and practical aspects of imaging research, but also a skill set for innovation translation, and b) dedicated translational imaging research (year 2) under the mentorship of highly-accomplished imaging pre-clinical and clinician scientists. With these needs and goals in mind, we are proposing TOP-TIER (Training OPportunities in Translational Imaging Education and Research), a clinician-scientist post-doctoral training program at Washington University (WU) in St. Louis to prepare resident and fellow trainees to bring preclinical imaging innovations into patients and to the practice of medicine.